Pathophysiologic basis of autonomic ganglionated plexus ablation in patients with atrial fibrillation

The intrinsic cardiac autonomic nervous system (ganglionated plexuses [GP]) plays a significant role in the initiation and maintenance of atrial fibrillation (AF) in both experimental models and AF patients. Left atrial GP, located in epicardial fat pads and the ligament of Marshall, contain afferent neurons from the atrial myocardium and the central autonomic nervous system, efferent neurons (cholinergic and adrenergic neurons), and interconnecting neurons, which allow communication between GP. Stimulation of the GP produces both parasympathetic stimulation (markedly shortens action potential duration) and sympathetic stimulation (increases calcium transient) in the pulmonary vein (PV) myocardium and atrial myocardium. In a canine model, GP stimulation resulted in early afterdepolarizations, and calcium transient triggered firing in the adjacent PV and initiated AF. Fractionated atrial potentials (FAP) were consistently located in the left atrium close to the stimulated GP. Ablation of the stimulated GP eliminated the FAP surrounding the GP. In patients with paroxysmal AF, epicardial and endocardial high-frequency stimulation produced a positive vagal response (transient AV block during AF and hypotension), allowing the identification and localization of five major left atrial GP (superior left GP, inferior left GP, Marshall tract GP, anterior right GP, inferior right GP). High-density electroanatomic maps of the left atrium and PVs obtained during AF showed the FAP are located in four main left atrial areas (left atrial appendage ridge FAP area, superior-left FAP area, inferoposterior FAP area, anterior-right FAP area). All five GP are located within one of the four FAP areas. In 63 patients with paroxysmal AF, GP ablation alone (before PV antrum isolation) significantly decreased the occurrence of PV firing (47/63 patients before ablation vs 9/63 patients after ablation, P <.01). GP ablation also decreased the inducibility of sustained AF (43/63 patients vs 23/63 patients, P <.01) and markedly reduced or eliminated the left atrial FAP areas.